Belimumab for Low Lymphocyte Count

Overseen By Irini Sereti, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Must not be taking: Glucocorticosteroids, Chemotherapy, Immunomodulants, others

Disqualifiers: HIV, Hepatitis, Tuberculosis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 13

Duration: 24 weeks

20 Participants Needed

Trial Summary

What is the purpose of this trial?

Background: People with Idiopathic CD4 lymphopenia (ICL) have lower numbers of a type of white blood cell called CD4 cells. White blood cells fight against infections. Low levels of CD4 cells may make a person more likely to get sick. There are no approved treatments for ICL. Researchers think a drug called belimumab may be able to help in specific situations. Objective: To see if belimumab is safe for people with ICL. Eligibility: People ages 18-70 who have ICL and are participating in NIH protocol 09-I-0102 (EPIC) Design: Participants will be screened with: Medical and medication history Physical exam Questionnaire about mental health and depression Blood and urine tests Participants will have a baseline visit. This will include some repeats of the screening tests. They may also have leukapheresis: Blood will be taken from a needle in one arm and passed through a machine that separates out the white blood cells. The rest of the blood will be returned through a needle in the other arm. Participants will receive 8 doses of belimumab through IV: A needle will insert a thin plastic tube into an arm vein. Belimumab will be given through the IV line. The first 3 doses will be given every 2 weeks. The other 5 will be given once every 4 weeks. Participants will have a physical exam and blood and urine tests at each dosing visit. They will be monitored for up to 4 hours after the infusion. Participants will have 3 follow-up visits, at around 8, 16, and 24 weeks after the last dose of belimumab. They will have a physical exam and blood and urine tests. Once they finish this protocol and they will continue to be followed under 09-I-0102 (EPIC study).

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are currently using systemic glucocorticosteroids or have used certain treatments like chemotherapy or immunomodulants in the past 6 months. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug Belimumab (Benlysta) for treating low lymphocyte count?

Belimumab (Benlysta) has been shown to effectively reduce B-cell levels and improve disease activity in patients with systemic lupus erythematosus (SLE), a condition where the immune system attacks its own tissues. This suggests it may help manage conditions involving abnormal immune responses, like low lymphocyte count. ^{1 2 3 4 5}

How is the drug belimumab unique for treating low lymphocyte count?

Belimumab is unique because it is a monoclonal antibody that specifically targets and inhibits a protein called B-lymphocyte stimulator, which is important for the survival and growth of B cells. This mechanism is different from other treatments, as it directly reduces the number of B cells, which may help in conditions with low lymphocyte counts. ^{1 3 4 5 6}

Research Team

Irini Sereti, M.D.

Principal Investigator

National Institute of Allergy and Infectious Diseases (NIAID)

Eligibility Criteria

Adults aged 18-70 with Idiopathic CD4 Lymphopenia (ICL), enrolled in NIH study 09-I-0102, and have low CD4 counts plus autoantibodies. They must use effective contraception and not be pregnant or breastfeeding. Exclusions include prior belimumab use, HIV, severe illnesses, certain infections, liver/kidney issues, recent vaccines, steroid use (except nasal/inhaler), cancer treatments within 6 months.

Inclusion Criteria

You must use birth control methods such as the pill, condoms, diaphragm, or an IUD to prevent pregnancy during the study.

My tests show positive for autoimmune antibodies.

Enrolled in study 09-I-0102

Exclusion Criteria

Pregnant

Hemoglobin < 8 g/dL

Serum creatinine > 1.5 times the upper limit of normal (ULN)

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Baseline

Baseline visit including repeats of screening tests and possible leukapheresis

1 day

1 visit (in-person)

Treatment

Participants receive 8 doses of belimumab through IV over 6 months

24 weeks

8 visits (in-person)

Follow-up

Participants have 3 follow-up visits at around 8, 16, and 24 weeks after the last dose

24 weeks

3 visits (in-person)

Treatment Details

Interventions

• Belimumab

Trial Overview The trial is testing the safety of a drug called belimumab for people with ICL. Participants will receive eight doses via IV over several weeks and undergo monitoring through physical exams as well as blood and urine tests during treatment and follow-up visits.

Participant Groups

Group I: Single arm, open-label Experimental Treatment 1 Intervention

Belimumab 10 mg/kg once every 2 weeks for 3 doses, and then once every 4 weeks for 5 doses, delivered via 1-hour intravenous (IV) infusion.

Belimumab is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Benlysta for:

• Systemic lupus erythematosus (SLE)

Approved in European Union as Benlysta for:

• Systemic lupus erythematosus (SLE)

Approved in Canada as Benlysta for:

• Systemic lupus erythematosus (SLE)

Approved in Japan as Benlysta for:

• Systemic lupus erythematosus (SLE)

Who Is Running the Clinical Trial?

National Institute of Allergy and Infectious Diseases (NIAID)

Lead Sponsor

Trials

3,361

Recruited

5,516,000+

Findings from Research

Benlysta (belimumab) is the first new drug approved for systemic lupus erythematosus (SLE) in 50 years, providing a new treatment option for patients with this complex disease.

Clinical trials suggest that Benlysta is effective in reducing SLE activity and flares in patients who are antinuclear antibody-positive, potentially allowing for lower doses of background medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belimumab and the clinical data. Shum, K., Askanase, A.[2021]

Belimumab, a targeted B-lymphocyte stimulator inhibitor, has shown significant efficacy in treating systemic lupus erythematosus (SLE) in late-stage clinical trials, particularly when combined with standard care, demonstrating statistically significant improvements over placebo.

The treatment has been well tolerated, with discontinuation rates and adverse events comparable to those of placebo, suggesting a favorable safety profile as it moves towards potential FDA approval.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belimumab: a BLyS-specific inhibitor for systemic lupus erythematosus. Wiglesworth, AK., Ennis, KM., Kockler, DR.[2013]

Belimumab is a monoclonal antibody that effectively targets and inhibits B-cell activating factor, leading to reduced B-cell levels and improved disease activity in patients with active systemic lupus erythematosus (SLE).

Clinical trials and post-marketing data indicate that belimumab is beneficial for lupus patients who continue to experience active disease despite receiving standard of care therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Post-marketing experiences with belimumab in the treatment of SLE patients. Askanase, AD., Yazdany, J., Molta, CT.[2015]

In a study of 17 female patients with lupus nephritis treated with belimumab for a median of 36 months, all patients experienced resolution of arthralgia and skin manifestations, indicating its efficacy in managing these symptoms.

Belimumab treatment led to normalization of proteinuria in three patients and allowed for the reduction or complete withdrawal of corticosteroids in 35% of patients, demonstrating its potential to improve kidney function and reduce reliance on steroids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belimumab may decrease flare rate and allow glucocorticoid withdrawal in lupus nephritis (including dialysis and transplanted patient). Binda, V., Trezzi, B., Del Papa, N., et al.[2021]

Belimumab (Benlysta®) is an effective treatment for adults with active, autoantibody-positive systemic lupus erythematosus (SLE), particularly for those who have high disease activity despite standard therapy.

In multinational trials, patients receiving belimumab showed significantly higher rates of achieving an SLE Responder Index response at 52 weeks compared to those receiving a placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belimumab: a guide to its use in systemic lupus erythematosus. Scott, LJ., Burness, CB., McCormack, PL.[2016]

In a study of 14 SLE patients treated with belimumab, significant reductions in total B cells, especially naive and transitional B cells, were observed after 6 months, correlating with decreased serum BLyS levels.

The reduction in total B cells within the first 6 months of therapy was significantly associated with improved disease activity (SLEDAI-2K) at 12 months, suggesting that monitoring B cell changes could help predict treatment response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association Between Changes in BLyS Levels and the Composition of B and T Cell Compartments in Patients With Refractory Systemic Lupus Erythematosus Treated With Belimumab. Regola, F., Piantoni, S., Lowin, T., et al.[2020]

References

1. United States pubmed.ncbi.nlm.nih.gov

Belimumab and the clinical data. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Belimumab: a BLyS-specific inhibitor for systemic lupus erythematosus. [2013]

3. United States pubmed.ncbi.nlm.nih.gov

Post-marketing experiences with belimumab in the treatment of SLE patients. [2015]

4. Italy pubmed.ncbi.nlm.nih.gov

Belimumab may decrease flare rate and allow glucocorticoid withdrawal in lupus nephritis (including dialysis and transplanted patient). [2021]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Belimumab: a guide to its use in systemic lupus erythematosus. [2016]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Association Between Changes in BLyS Levels and the Composition of B and T Cell Compartments in Patients With Refractory Systemic Lupus Erythematosus Treated With Belimumab. [2020]